OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

Objective To investigate the epidemiological characteristics of lymphoma mortality and potential years of life lost among Wuhan residents, and to provide a scientific basis for the prevention and control of lymphoma. Methods Data on lymphoma deaths among residents in Wuhan from 2010 to 2019 were collected from the population-based Wuhan Mortality Surveillance System. Joinpoint regression model was used to evaluate the trends in age-standardized mortality rates and potential years of life lost due to lymphoma among the residents of different ages and genders. Potential years of life lost rate was used to assess the disease burden. Results There were 4 055 deaths (2481in male and 1 574 in female) from major kidney diseases in Wuhan residents between 2010 to 2019, with an age-standardized mortality rate of 5.11/100 000. The mortality rate of major kidney diseases showed an upward trend with increasing age. Between 2010 and 2019, the age-standardized mortality rates of the multiple myeloma and non-Hodgkin lymphoma were significantly increased (APC=6.924%, APC=1.407%, P＜0.05), and the potential years of life lost rate of non-Hodgkin lymphoma in female were significantly increased (APC=7.935%，P＜0.05). Conclusion From 2010 to 2019, the mortality rate of lymphoma among residents of Wuhan City shows an upward trend, especially for multiple myeloma and non-Hodgkin lymphoma. The disease burden of multiple myeloma shows an increasing trend in the female population, suggesting the need to take corresponding preventive and control measures.

Objective To analyze the impact of digital conversion of screen-film chest radiographs on image quality in patients with pneumoconiosis. Methods Ten high-kilovoltage screen-film chest radiographs from pneumoconiosis patients were digitally converted using three devices, including a digital single-lens reflex camera, a smartphone, and a medical film scanner. The image quality and optical density values before and after image adjustment were compared across different image formats. Results Before adjustment, among the 30 JPEG images, 24 had diagnostic defect areas and 26 had unqualified optical density values. In RAW format, optical density values were not qualified in 18 out of 30 images. In DICOM format, optical density values were not qualified in nine of ten images. After adjustment, optical density values were not qualified in 13 JPEG images, 12 RAW images, and one DICOM image. Comparisons of chest radiograph quality grade distributions before and after adjustment showed significant differences for all three image formats (all P<0.05). Conclusion After being digitally converted by taking images in RAW format with digital photographic equipment and undergoing post-processing adjustment, the quality of screen-film chest radiographs for pneumoconiosis can meet the diagnostic requirements.

OBJECTIVE: To investigate the accuracy and safety of pedicle screw placement using 3D-printed auxiliary guides in scoliosis correction surgery for adolescents. METHODS: A retrospective analysis was conducted on the clinical data of 51 patients who underwent posterior scoliosis correction surgery from January 2020 to March 2023. Among them, there were 35 cases of adolescent idiopathic scoliosis and 16 cases of congenital scoliosis. The patients were divided into two groups based on the auxiliary tool used:the 3D-printed auxiliary guide screw placement group (3D printing group) and the free-hand screw placement group (free-hand group, without auxiliary tools). The 3D printing group included 32 patients (12 males and 20 females) with an average age of (12.59±2.60) years;the free-hand group included 19 patients (7 males and 12 females) with an average age of (14.58±3.53) years. The two groups were compared in terms of screw placement accuracy and safety, spinal correction rate, intraoperative blood loss, number of intraoperative fluoroscopies, operation time, hospital stay, and preoperative and last follow-up scores of the Scoliosis Research Society-22 (SRS-22) questionnaire. RESULTS: A total of 707 pedicle screws were placed in the two groups, with 441 screws in the 3D printing group and 266 screws in the free-hand group. All patients in both groups successfully completed the surgery. There was a statistically significant difference in operation time between the two groups (P<0.05). The screw placement accuracy rate of the 3D printing group was 95.46% (421/441), among which the Grade A placement rate was 89.34% (394/441);the screw placement accuracy rate of the free-hand group was 86.47% (230/266), with a Grade A placement rate of 73.31% (195/266). There were statistically significant differences in the accuracy of Grade A, B, and C screw placements between the two groups (P<0.05), while no statistically significant differences were observed in intraoperative blood loss, number of fluoroscopies, correction rate, or hospital stay (P>0.05). In the SRS-22 questionnaire scores, the scores of functional status and activity ability, self-image, mental status, and pain of patients in each group at the last follow-up were significantly improved compared with those before surgery (P<0.05), but there were no statistically significant differences in all scores between the two groups (P>0.05). CONCLUSION In scoliosis correction surgery, compared with traditional free-hand screw placement, the use of 3D-printed auxiliary guides for screw placement significantly improves the accuracy and safety of screw placement and shortens the operation time.
Humans ; Male ; Scoliosis/surgery* ; Female ; Adolescent ; Printing, Three-Dimensional ; Retrospective Studies ; Pedicle Screws ; Child

OBJECTIVE: To investigate the characteristics of gut microbiota changes in patients with acute myeloid leukemia (AML) undergoing induction chemotherapy and to explore the relationship between infectious complications and gut microbiota. METHODS: Fecal samples were collected from 37 newly diagnosed AML patients at four time points: before induction chemotherapy, during chemotherapy, during the neutropenic phase, and during the recovery phase. Metagenomic sequencing was used to analyze the dynamic changes in gut microbiota. Correlation analyses were conducted to assess the relationship between changes in gut microbiota and the occurrence of infectious complications. RESULTS: During chemotherapy, the gut microbiota α-diversity (Shannon index) of AML patients exhibited significant fluctuations. Specifically, the diversity decreased significantly during induction chemotherapy, further declined during the neutropenic phase (P < 0.05, compared to baseline), and gradually recovered during the recovery phase, though not fully returning to baseline levels.The abundances of beneficial bacteria, such as Firmicutes and Bacteroidetes, gradually decreased during chemotherapy, whereas the abundances of opportunistic pathogens, including Enterococcus, Klebsiella, and Escherichia coli, progressively increased.Analysis of the dynamic changes in gut microbiota of seven patients with bloodstream infections revealed that the bloodstream infection pathogens could be detected in the gut microbiota of the corresponding patients, with their abundance gradually increasing during the course of infection. This finding suggests that bloodstream infections may be associated with opportunistic pathogens originating from the gut microbiota.Compared to non-infected patients, the baseline samples of infected patients showed a significantly lower relative abundance of Bacteroidetes (P < 0.05). Regression analysis indicated that Bacteroidetes abundance is an independent predictive factor for infectious complications (P < 0.05, OR =13.143). CONCLUSION During induction chemotherapy in AML patients, gut microbiota α-diversity fluctuates significantly, and the abundance of opportunistic pathogens increase, which may be associated with bloodstream infections. Patients with lower baseline Bacteroidetes abundance are more prone to infections, and its abundance can serve as an independent predictor of infectious complications.
Humans ; Gastrointestinal Microbiome ; Leukemia, Myeloid, Acute/microbiology* ; Induction Chemotherapy ; Feces/microbiology* ; Male ; Female ; Middle Aged

This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

Objective:To investigate the early predictive value of ECG PR interval for the risk of coronary heart disease(CHD) in patients with T2DM.Methods:A total of 7 886 participants from Guiyang who enrolled in the REACTION study between May and August 2011 were included. Baseline data were collected, and participants were followed for 10 years to monitor the occurrence of CHD. Logistic regression was used to identify risk factors for CHD, and a Cox proportional hazards model was employed to assess the predictive value of the PR interval for CHD incidence. Results:Over 10 years of follow-up, the overall incidence of CHD was 4.22%(245/5 812). The incidence was significantly higher in the T2DM group(7.57%, 96/1 268) than in the non-T2DM(3.28%, 149/4 544), and the shortened PR group(3.19%, 36/1 130; all P<0.05). Multiple logistic regression analysis identified both T2DM and prolonged PR interval as significant risk factors for CHD, with HR(95% CI) of 1.98(1.64-2.42) and 1.07(1.04-1.10), respectively(both P<0.01). The Cox proportional hazards model further revealed that the risk of CHD was significantly higher in the prolonged PR group than in the normal PR group, with an HR of 2.82(95% CI 2.34-3.12, P<0.01). Subgroup analysis showed that the risk of CHD was elevated in the non-T2DM with prolonged PR group, T2DM with normal PR group, and T2DM with prolonged PR group compared to the non-T2DM with normal PR group, with HRs(95% CI) of 1.43(1.14-1.82), 2.16(1.78-2.56), and 5.24(3.12-7.94), respectively. A significant interaction was observed between T2DM status and PR prolongation in predicting CHD risk(all P<0.01). Conclusions:Both T2DM and prolonged PR interval are independent risk factors for 10-year CHD incidence. Moreover, an interaction exists between T2DM and prolonged PR interval in predicting CHD risk. The PR interval may serve as an early predictor of CHD risk in patients with T2DM.

Objective:To investigate the clinical manifestations, therapeutic strategies and prognostic outcomes in pediatric patients with severe Mycoplasma pneumoniae pneumonia (SMPP) complicated by cardiac thrombosis. Methods:This case series study retrospectively analyzed 15 pediatric patients with SMPP complicated by cardiac thrombosis. The patients was recruited from the Department of Pediatric Respiratory Medicine at Shandong Provincial Hospital Affiliated to Shandong First Medical University between July 2018 and January 2025. Comprehensive clinical data and follow-up information were collected.Results:Among the 15 children, 10 were male and 5 were female, and the age of onset was 8.0 (6.3, 10.0) years. All 15 children presented with fever and cough, while additional symptoms included dyspnea in 7 cases, chest pain in 6 cases, hemoptysis in 3 cases, and chest tightness in 1 case. The white blood cell count was 11.7 (9.5, 15.9)×10 9/L, C-reactive protein was 31.6 (17.5, 64.8) mg/L and lactate dehydrogenase was 548.2 (410.4, 768.3) U/L. A total of 14 children underwent testing for the Mycoplasma pneumoniae drug resistance genes 2063A>G and 2064A>G, of which 13 tested positive. The plasma D-dimer levels of 15 children were 8.77 (7.23, 12.50) mg/L, all of which were higher than normal. Among the 15 children, 5 had decreased activity of anticoagulant proteins (protein C, protein S, antithrombin Ⅲ), and 8 tested positive for antiphospholipid antibodies. Chest CT scans of all 15 children showed pulmonary consolidation and (or) atelectasis, with pleural effusion present in 12 cases. In the 15 children, thrombosis was detected at 14.0 (11.0, 18.0) days after the onset of illness. The locations of cardiac thrombosis included the right ventricle in 9 cases, the right atrium in 5 cases, and the left atrium in 1 case. Additionally, 10 cases had pulmonary vascular embolism, comprising 9 cases of pulmonary artery thrombosis and 1 case of pulmonary vein thrombosis. After anticoagulant treatment, cardiac thrombi disappeared in 10 children. Five children who did not show improvement with anticoagulation underwent surgical thrombectomy. In the follow-up of 15 children, lung imaging basically returned to normal, with no major hemorrhagic events or other adverse events. Conclusions:In children with Mycoplasma pneumoniae pneumonia, the presence of clinical symptoms such as shortness of breath, chest pain and hemoptysis, along with elevated plasma D-dimer levels, should raise suspicion for the possibility of cardiac thrombosis. SMPP complicated by cardiac thrombosis, prognosis is good following anticoagulation or surgical treatment.

Objective To observe the value of conventional MRI and diffusion weighted imaging(DWI)for differentiating soft tissue lymphoma(STL)and soft tissue sarcoma(STS).Methods Conventional MRI and DWI data of 25 cases of STL(STL group)and 38 cases of STS(STS group)were retrospectively analyzed.MRI features being statistically different between groups were included in logistic regression analysis to screen the independent risk factors of STL and to evaluate the sensitivity,specificity and accuracy of their combination for predicting STL.Receiver operating characteristic curve was generated,the area under the curve(AUC)was calculated to assess the diagnostic efficacy of the mean apparent diffusion coefficient(ADCmean),the minimum apparent diffusion coefficient(ADCmin),the maximum apparent diffusion coefficient(ADCmax)values for distinguishing STL from STS.Results Slightly hyperintensity on T1WI,non-necrosis,involvement of multiple muscle groups and homogeneous enhancement were all independent risk factors of STL(all P＜0.05).The sensitivity,specificity and accuracy of their combination for predicting STL was 72.00％(18/25),89.47％(34/38)and 82.54％(52/63),respectively.ADCmean,ADCmin and ADCmax values of STL was(1.06±0.18)× 10-3,(0.77±0.14)×10-3 and(1.47±0.31)× 10-3mm2/s,respectively,all lower than those of STS([1.31±0.17]× 10-3,[1.02±0.23]× 10-3 and[1.64±0.16]× 10-3 mm2/s;t=-4.829--2.498,all P＜0.05).The AUC of ADCmean,ADCmin and ADCmax values and their combination for differential diagnosis of STL and STS was 0.845,0.844,0.683 and 0.877,respectively.Conclusion Conventional MRI features,including T1WI signal intensity,necrosis,involvement of multiple muscle groups and enhancement pattern,along with ADCmean and ADCmin values derived from DWI contributed to differentiating STL and STS.